Dosing and uses of Sustiva (efavirenz)
Adult dosage forms and strengths
capsule
- 50mg
- 200mg
tablet
- 600mg
HIV Infection
Indicated in combination with other antiretroviral agents for HIV-1 infection
600 mg PO qDay; used in combination with protease inhibitor and/or NRTIs
Dosage modifications
Coadministration with voriconazole: Increase voriconazole maintenance dose to 400 mg q12hr and decrease efavirenz dose to 300 mg qDay (using capsule formulation)
Coadministration with rifampin: If weight >50 kg, increase efavirenz to 800 mg qDay
Renal impairment: No dosage adjustment needed
Hepatic impairment
- Mild (Child-Pugh Class A): Dose adjustment not necessary; use caution
- Moderate-to-severe (Child Pugh Class B or C): Not recommended
Administration
Swallow capsule or table whole; do not break tablet
Take only on empty stomach, preferably at bedtime
Capsule sprinkle method
- If unable to swallow capsule or tablet, capsule contents may be mixed with a small amount of food (ie ~2 teaspoonfuls) or room temperature formula (ie, 10 mL)
- Consume food/formula mixture within 30 minutes of mixing
- Do not consume additional food for at least 2 hr after administration
Pediatric dosage forms and strengths
capsule
- 50mg
- 200mg
tablet
- 600mg
HIV Infection
Indicated in combination with other antiretroviral agents for HIV-1 infection in pediatric patients >3 months old and weighing ≥3.5 kg
<3 months: Safety and efficacy not established
≥3 months
- 3.5 kg to <5 kg: 100 mg PO qDay
- 5 to <7.5 kg: 150 mg PO qDay
- 7.5 to <15 kg: 200 mg PO qDay
- 15 to <20 kg: 250 mg PO qDay
- 20 to <25 kg: 300 mg PO qDay
- 25 to <32.5 kg: 350 mg PO qDay
- 32.5 to <40 kg: 400 mg PO qDay
- ≥40 kg: 600 mg PO qDay
Dosage modifications
Coadministration with voriconazole: If weight >40 kg and age >12 yr, increase voriconazole maintenance dose to 400 mg q12hr and decrease efavirenz dose to 300 mg qDay (using capsule formulation)
Coadministration with rifampin: If weight >40 kg, increase efavirenz to 800 mg qDay
Renal impairment: No dosage adjustment needed
Hepatic impairment
- Mild (Child-Pugh Class A): Dose adjustment not necessary; use caution
- Moderate-to-severe (Child Pugh Class B or C): Not recommended
Administration
Swallow capsule or table whole; do not break tablet
Take only on empty stomach, preferably at bedtime
Capsule sprinkle method
- If unable to swallow capsule or tablet, capsule contents may be mixed with a small amount of food (ie ~2 teaspoonfuls) or room temperature formula (ie, 10 mL)
- Consume food/formula mixture within 30 minutes of mixing
- Do not consume additional food for at least 2 hr after administration
Sustiva (efavirenz) adverse (side) effects
>10%
Total cholesterol increased (20-40%)
Diarrhea (3-14%, children up to 39%)
HDL increased (25-35%)
Dizziness (28.1%)
Rash (5-26%)
Fever (children 21%)
Depression (19%)
Insomnia (16.3%)
Cough (children 16%)
Vomiting (3-12%)
Anxiety (2-13%)
Nausea (2-12%)
1-10%
Neutropenia (2-10%)
Pruitis (9%)
Impaired concentration (8.3%)
Transaminases increased (2-8%)
Somnolence (7.0%)
Abnormal dreams (6.2%)
Amylase increased (6%)
Hyperglycemia (2-5%)
Dyspepsia (4%)
Abdominal pain (2-3%)
Anorexia (2%)
Hallucinations (1.2%)
Postmarketing Reports
Serious psychiatric events: severe depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4% ), manic reactions (0.2%)
Stevens-Johnson syndrome
Erythema multiforme
Exfoliative dermatitis
Hepatotoxicity
Pancreatitis
Cardiac arrhythmias
Prolonged sedation, or respiratory depression
Vertigo
Warnings
Contraindications
Previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions)
Cautions
Hepatic impairment; not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine whether dose adjustment is necessary
Monitor liver function tests before and during treatment in patients with underlying hepatic disease, including hepatitis B or C coinfection, marked transaminase elevations, or who are taking medications associated with liver toxicity; among reported cases of hepatic failure, a few occurred in patients with no pre-existing hepatic disease; weigh risk/benefit if AST/ALT >5 xULn
Redistribution of fat may occur (cushingoid appearance)
Risk of serious psychiatric events (eg, depression, suicidality, paranoia, manic episodes); immediate medical evaluation recommended for serious psychiatric symptoms such as severe depression or suicidal ideation
CNS symptoms reported (eg, dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, and hallucinations); nervous system symptoms (NSS) are frequent and usually begin 1-2 days after initiating therapy and resolve in 2-4 weeks; dosing at bedtime may improve tolerability; NSS are not predictive of onset of psychiatric symptoms
Risk of skin rash - discontinue if severe rash associated wtih blistering, desquamation, mucosal involvement, or fever
Use caution in history of seizures
Total cholesterol and triglyceride elevations may occur; monitor before therapy and periodically thereafter
Women should avoid pregnancy; use 2 forms of contraception including a barrier method; postmarketing reports of contraceptive failure in patients on efavirenz while on an implantable hormonal contraceptive; avoid administration in first trimester of pregnancy as fetal harm may occur
Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs; immune reconstitution syndrome may necessitate further evaluation and treatment
Autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment
Not for use as a single agent or add on as a sole agent to a failing regimen; consider potential for cross-resistance when choosing other agents
Not recommended with ATRIPLA, which contains efavirenz, emtricitabine, and tenofovir disoproxil fumarate, unless needed for dose adjustment when coadministered with rifampin
Consider alternatives in patients taking other medications with known risk of Torsade de Pointes or in patients at higher risk of Torsade de Pointes
Interactions
- Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A
- Likewise, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or CYP2B6
- The most prominent effect of efavirenz at steady-state is induction of CYP3A and CYP2B6
Pregnancy and lactation
Pregnancy category: d
Lactation: It is not known whether efavirenz is excreted in milk. It should not be administered to nursing mothers. The CDC advises HIV-infected women not to breast-feed to avoid postnatal transmission of HIV.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sustiva (efavirenz)
Mechanism of action
Non-nucleoside reverse transcriptase inhibitor (NNRTI) against HIV-1
Absorption
Peak Plasma Time: 2.5-4 hr
Metabolism
Metabolized by liver CYP3A4 and CYP2B6
Inhibits: CYP2C9; CYP2C19, and CYP3A4 (in vitro)
Induces: CYP3A4 (in vivo)
Elimination
Half-Life: 41 hr ± 20 hr
Excretion: Urine (14-34%); feces (16-61%)
Distribution
Protein binding: 99% (albumin)
